Human T-Cell Biology in a Mouse Environment

  • Nicolas Legrand
  • Hergen Spits


After decades of incremental optimization efforts, mouse models of human hematopoiesis supporting de novo human hematopoietic cell development in situ have been obtained. Although these new humanized mouse models represent a major achievement, they still exhibit several limitations and do not fully support optimal human leukocyte biology. Still, they provide clues on what could be the milestones to target for the next generation of humanized mouse models of the immune system, especially when dealing with the functionality of the human hematopoietic cells in such a setting. In this chapter, we specifically address human T-cell development and homeostasis in a selection of recent human immune system (HIS) mouse models, discuss their intrinsic limitations for prospective study of human T-cell biology, and speculate on future areas of HIS mouse model improvement.


Humanized mouse models Human immune system mice BRG BRGS NSG NOG BLT Human hematopoiesis Hematopoietic stem and progenitor cell transplantation T lymphocytes 



Bone marrow, liver, thymus


BALB/c Rag2−/− IL-2Rγc −/−


BALB/c Rag2−/− IL-2Rγc −/− SIRPαNOD


Dendritic cells


Follicular dendritic cells


Fetal liver


Fibroblastic reticular cells


Graft-versus-host disease


Human immune system


Human hematopoietic stem and progenitor cells


Human thymus seeding progenitor cells


Immature single positive


Lymph node


Lymphoid tissue inducer


Nonobese diabetic




NOD.Cg-Prkdcscid IL2rg tmlWjl /Sz


Severe combined immuno-deficiency


T follicular helper


Umbilical cord blood



We thank Dr. Mireille Centlivre for valuable suggestions and critical reading of the manuscript.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.AXENISParisFrance
  2. 2.Tytgat Institute for Liver and Intestinal Research, AMC-UvAAmsterdamThe Netherlands

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